Yan Borné1, Martin Söderholm2, Lars Barregard3, Björn Fagerberg4, Margaretha Persson2, Olle Melander2, Frank Thévenod5, Bo Hedblad2, Gunnar Engström2. 1. Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms Gata 35, Lund University, Malmö, SE 205 02 Malmö yan.borne@med.lu.se. 2. Department of Clinical Sciences in Malmö, CRC, Jan Waldenströms Gata 35, Lund University, Malmö, SE 205 02 Malmö. 3. Occupational and Environmental Medicine, Sahlgrenska University Hospital and University of Gothenburg, Po Box 414, SE 405 30. 4. Department of Molecular and Clinical Medicine, Wallenberg Laboratory for Cardiovascular and Metabolic Research, University of Gothenburg, and Sahlgrenska University Hospital, SE 413 45 Gothenburg, Sweden. 5. Department of Physiology, Pathophysiology & Toxicology and ZBAF (Centre for Biomedical Education and Research), Faculty of Health - School of Medicine, Witten/Herdecke University, Stockumer Str 12 (Thyssenhaus), D 58453 Witten, Germany.
Abstract
BACKGROUND: Cadmium is a non-essential toxic metal with multiple adverse health effects. Exposure in the general population occurs by smoking and diet. Cadmium in erythrocytes is a valid biomarker of exposure and body burden of cadmium. OBJECTIVES: We aimed to identify genetic variants related to concentrations of cadmium in erythrocytes. METHODS: Erythrocyte cadmium was analyzed in 4432 individuals (1728 never smokers) from the Swedish population-based Malmö Diet and Cancer cohort. Genotyping was performed using the Illumina HumanOmniExpressExome Bead chip with genome-wide coverage. Genome wide analyses were performed in the whole sample and in never smokers. RESULTS: No single nucleotide polymorphism (SNP) reached a genome-wide significant association with erythrocyte cadmium in the whole sample. However, in never smokers, 14 variants showed genome-wide significant relationships with erythrocyte cadmium after adjusting for age and sex. Thirteen variants were in linkage disequilibrium on chromosome 8q13.3 in the XKR9 and LACTB2 genes. The lead SNP on 8q13.3 was rs12681420 (minor allele G, minor allele frequency [MAF] = 0.46, β: -0.11, P = 3.48 × 10-11), an intron variant within the XKR9 gene. The other significant locus, rs17574271 (minor allele C, MAF = 0.09, β: 0.17, P = 6.18 × 10-9), was an intron variant within the DLGAP1 gene at chromosome 18p11.31. CONCLUSION: This genome-wide study of never smokers from the general population identified two independent regions related to erythrocyte cadmium. The strongest locus covers the XKR9 and LACTB2 genes, which both could have related functions in cadmium absorption and metabolism. Replication studies are needed to confirm the findings and mechanisms should be further investigated.
BACKGROUND:Cadmium is a non-essential toxic metal with multiple adverse health effects. Exposure in the general population occurs by smoking and diet. Cadmium in erythrocytes is a valid biomarker of exposure and body burden of cadmium. OBJECTIVES: We aimed to identify genetic variants related to concentrations of cadmium in erythrocytes. METHODS: Erythrocyte cadmium was analyzed in 4432 individuals (1728 never smokers) from the Swedish population-based Malmö Diet and Cancer cohort. Genotyping was performed using the Illumina HumanOmniExpressExome Bead chip with genome-wide coverage. Genome wide analyses were performed in the whole sample and in never smokers. RESULTS: No single nucleotide polymorphism (SNP) reached a genome-wide significant association with erythrocyte cadmium in the whole sample. However, in never smokers, 14 variants showed genome-wide significant relationships with erythrocyte cadmium after adjusting for age and sex. Thirteen variants were in linkage disequilibrium on chromosome 8q13.3 in the XKR9 and LACTB2 genes. The lead SNP on 8q13.3 was rs12681420 (minor allele G, minor allele frequency [MAF] = 0.46, β: -0.11, P = 3.48 × 10-11), an intron variant within the XKR9 gene. The other significant locus, rs17574271 (minor allele C, MAF = 0.09, β: 0.17, P = 6.18 × 10-9), was an intron variant within the DLGAP1 gene at chromosome 18p11.31. CONCLUSION: This genome-wide study of never smokers from the general population identified two independent regions related to erythrocyte cadmium. The strongest locus covers the XKR9 and LACTB2 genes, which both could have related functions in cadmium absorption and metabolism. Replication studies are needed to confirm the findings and mechanisms should be further investigated.
Authors: Maria Grau-Perez; V Saroja Voruganti; Poojitha Balakrishnan; Karin Haack; Walter Goessler; Nora Franceschini; Josep Redón; Shelley A Cole; Ana Navas-Acien; Maria Tellez-Plaza Journal: Environ Pollut Date: 2021-02-11 Impact factor: 8.071